Journal of the Neurological Sciences 340 (2014) 130–132
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Magnetic resonance imaging reveals Creutzfeldt–Jakob disease in a patient with apparent dementia with Lewy bodies Georgios Tsivgoulis a,b,⁎, Anastasios Bonakis a, Matilda A. Papathanasiou c, Maria Chondrogianni a, Sokratis G. Papageorgiou a, Konstantinos Voumvourakis a, Leonidas Stefanis a a b c
Second Department of Neurology, University of Athens, School of Medicine, “Attikon” University Hospital, Athens, Greece International Clinical Research Center, St. Anne's University Hospital Brno, Czech Republic Second Department of Radiology, University of Athens, School of Medicine, “Attikon” University Hospital, Athens, Greece
a r t i c l e
i n f o
Article history: Received 26 January 2014 Received in revised form 4 March 2014 Accepted 5 March 2014 Available online 11 March 2014 Keywords: Creutzfeldt–Jakob disease MRI Dementia with Lewy bodies Neuroimaging
a b s t r a c t The differential diagnosis of dementia with Lewy bodies (DLB) and sporadic Creutzfeldt–Jakob disease (CJD) may be challenging. Patients with the original diagnosis of possible CJD may occasionally prove to have a pathological diagnosis of DLB, while other cases may fulﬁll the diagnostic clinical criteria for DLB but subsequent clinical course, cerebrospinal ﬂuid (CSF) and neuropathology ﬁndings necessitate diagnostic revision to CJD. We describe a 79-year old patient recently diagnosed with dementia with Lewy bodies (DLB) on the basis of subacute cognitive decline, visual hallucinations and Parkinsonian features, who presented with increasing agitation. Brain neuroimaging with MRI raised the diagnostic suspicion of CJD and subsequent diagnostic work-up with electroencephalography (EEG) and CSF analysis led to the establishment of CJD diagnosis. The present case highlights the clinical utility of novel diagnostic CJD criteria that also incorporate neuroimaging ﬁndings in the diagnostic CJD panel. © 2014 Elsevier B.V. All rights reserved.
2. Case description
The differential diagnosis of dementia with Lewy bodies (DLB) and sporadic Creutzfeldt–Jakob disease (CJD) may be challenging. Patients with the original diagnosis of possible CJD may occasionally prove to have a pathological diagnosis of DLB [1,2]. Conversely, certain cases may fulﬁll the diagnostic clinical criteria for DLB but subsequent clinical course, cerebrospinal ﬂuid (CSF) and neuropathology ﬁndings necessitated diagnostic revision to CJD [3,4]. We describe a patient fulﬁlling the clinical diagnostic criteria for DLB in whom brain neuroimaging raised the diagnostic suspicion of CJD and prompted further diagnostic work-up that led to the establishment of CJD diagnosis. We also review the phenotypic overlap between DLB and CJD which may cause clinical misdiagnosis and highlight the clinical utility of novel diagnostic CJD criteria that also incorporate neuroimaging ﬁndings in the diagnostic panel of CJD.
A 79-year-old man recently diagnosed with DLB on the basis of subacute cognitive decline (with early impairment in attention and in executive as well as visuospatial function in the absence of memory impairment), recurrent well-formed visual hallucinations (involving animals and landscapes) and spontaneous Parkinsonian motor signs (symmetric bradykinesia, cogwheeling, reduced range of facial expression and stooped posture) presented with increasing agitation to an outside institution. More speciﬁcally, the patient exhibited neuroleptic sensitivity following intramuscular administration of haloperidol at the outside institution with increasing restlessness and aggressiveness and was transferred for further evaluation in our department. His relatives reported that cognitive impairment manifested during the past ﬁve months and noted substantial ﬂuctuations in his cognitive status. Clinical examination conﬁrmed the diagnosis of DLB on the basis of the following criteria: dementia, recurrent well-formed visual hallucinations and spontaneous Parkinsonian motor signs. Cognitive status was assessed using modiﬁed Mini-Mental State Examination, Clock Drawing Test and Clinical Dementia Rating Scale. Neurological examination disclosed no evidence of myoclonus, cerebellar or pyramidal sings. Brain Magnetic Resonance Imaging (MRI) showed diffusion restriction in bilateral caudate nuclei, suggesting acute cerebral infarctions. He was transferred to our department for further diagnostic evaluation.
⁎ Corresponding author at: Second Department of Neurology, University of Athens, School of Medicine, Iras 39, Gerakas Attikis, Athens 15344, Greece. Tel.: + 30 6937178635; fax: +30 2105832471. E-mail address: [email protected]
http://dx.doi.org/10.1016/j.jns.2014.03.010 0022-510X/© 2014 Elsevier B.V. All rights reserved.
G. Tsivgoulis et al. / Journal of the Neurological Sciences 340 (2014) 130–132
Fig. 1. Brain MR with axial diffusion-weighted imaging (DWI; Panels A & B) and apparent diffusion coefﬁcient (ADC; Panel C) sequences showing right frontal opercular, parietal and occipital ribboning (yellow arrowheads) that is depicted as gyriform hyperintense cortical areas. Bilateral diffusion restriction is also noted in the head of caudate nucleus in DWI (red arrowheads) and ADC (green arrowheads) sequences.
A review of available neuroimaging studies indicated abnormalities typical of CJD: right frontal opercular, parietal and occipital ribboning that was depicted as gyriform hyperintense cortical areas as well as bilateral caudate diffusion restriction (Fig. 1). The diagnosis of probable CJD was conﬁrmed by electroencephalography (periodic sharp wave complexes with duration of 100–600 ms and intercomplex interval of 0.5–2 s; Fig. 2) and cerebrospinal-ﬂuid analysis (positive 14-3-3 protein).
3. Discussion CJD may be initially misdiagnosed as DLB [2–4]. This may result from overlap of clinical features or investigation ﬁndings . For example, EEG periodic sharp wave complexes, though highly sensitive and speciﬁc for the diagnosis of pathologically conﬁrmed CJD , are not pathognomonic and may occasionally occur in pathologically conﬁrmed DLB . Brain MRI has recently attained a signiﬁcant diagnostic role in suspected
Fig. 2. Electroencephalogram disclosing typical period sharp wave complexes (duration of 100–600 ms) with intercomplex interval of 0.5.
G. Tsivgoulis et al. / Journal of the Neurological Sciences 340 (2014) 130–132
cases of CJD [8,9]. More speciﬁcally, brain MRI ﬁndings have been incorporated in the new diagnostic CJD criteria that have been recently proposed . DWI is the most sensitive neuroimaging study for early CJD detection that may reveal the following characteristic ﬁndings [5,8,9]: (i) basal ganglia hyperintensities coupled with diffusion restriction on ADC (apparent diffusion coefﬁcient) maps, (ii) hyperintensity of frontal, temporal, occipital, insular, and/or parietal regions referred to as cortical ribboning, (iii) symmetrical hyperintensity in the pulvinar nuclei of the thalamus (pulvinar sign), and/or symmetrical hyperintensity both in the pulvinar and in dorsomedial thalamic nuclei (“hockeystick” sign). It has recently been shown that DWI ﬁndings may assist the clinician in accurately differentiating CJD from other rapidly progressive dementia with a sensitivity and speciﬁcity N90% . The present case highlights the diagnostic utility of MRI in establishing the diagnosis of CJD in an accurate and timely fashion in a patient initially misdiagnosed as DLB. This report lends support to current observations  detecting higher diagnostic yield of newly developed CJD criteria that also incorporate MRI ﬁndings in comparison to the standard WHO (World Health Organization) criteria  that do not include neuroimaging ﬁndings.
Authorship contribution statement Georgios Tsivgoulis: Drafting and revising the manuscript. Anastasios Bonakis: Data collection (EEG Interpretation) and critical comments during manuscript revision. Matilda A. Papathanasiou: Data collection (review of neuroimaging ﬁndings) and critical comments during manuscript revision. Maria Chondrogianni: Data collection and critical comments during manuscript revision. Sokratis G. Papageorgiou: Data collection (neuropsychological evaluation) and critical comments during manuscript revision. Konstantinos Voumvourakis: Critical comments during manuscript revision. Leonidas Stefanis: Drafting and revising the manuscript.
Study funding Dr Georgios Tsivgoulis has been supported by European Regional Development Fund — Project FNUSA-ICRC (No. CZ.1.05/1.1.00/02.0123). Disclosures All authors report no disclosures. Acknowledgments None. References  Collie DA, Summers DM, Sellar RJ, Ironside JW, Cooper S, Zeidler M, et al. Diagnosing variant Creutzfeldt–Jakob disease with the pulvinar sign: MR imaging ﬁndings in 86 neuropathologically conﬁrmed cases. AJNR Am J Neuroradiol 2003;24:1560–9.  Doran M, Larner AJ. EEG ﬁndings in dementia with Lewy bodies causing diagnostic confusion with sporadic Creutzfeldt–Jakob disease. Eur J Neurol 2004;11:838–41.  Kraemer C, Lang K, Weckesser M, Evers S. Creutzfeldt–Jacob disease misdiagnosed as dementia with Lewy bodies. J Neurol 2005;252:861–86.  Larner AJ. Re: Creutzfeldt–Jacob disease misdiagnosed as dementia with Lewy bodies. J Neurol 2006;253:960.  Newey CR, Sarwal A, Wisco D, Alam S, Lederman RJ. Variability in diagnosing Creutzfeldt–Jakob disease using standard and proposed diagnostic criteria. J Neuroimaging 2013;23:58–63.  Tschampa HJ, Neumann M, Zerr I, Henkel K, Schröter A, Schulz-Schaeffer WJ, et al. Patients with Alzheimer's disease and dementia with Lewy bodies mistaken for Creutzfeldt–Jakob disease. J Neurol Neurosurg Psychiatry 2001;71:33–9.  Zerr I, Pocchiari M, Collins S, Brandel JP, de Pedro Cuesta J, Knight RS. Analysis of EEG and CSF 14-3-3 proteins as aids to the diagnosis of Creutzfeldt–Jakob disease. Neurology 2000;55:811–5.  Vitali P, Maccagnano E, Caverzasi E, Henry RG, Haman A, Torres-Chae C, et al. Diffusion-weighted MRI hyperintensity patterns differentiate CJD from other rapid dementias. Neurology 2011;76:1711–9.  Zerr I, Kallenberg K, Summers DM, Romero C, Taratuto A, Heinemann U, et al. Updated clinical diagnostic criteria for sporadic Creutzfeldt–Jakob disease. Brain 2009;132:2659–68.  WHO. Global surveillance, diagnosis and therapy of human transmissible spongiform encephalopathies: report of a WHO consultation. World Health Organization: an Emerging and Other Communicable Diseases, Surveillance and Control; 1998.